A multi-omics spatial framework for host-microbiome dissection within the intestinal tissue microenvironment

Bokai Zhu, Yunhao Bai, Yao Yu Yeo, Xiaowei Lu, Xavier Rovira-Clavé, Han Chen, Jason Yeung, Dingani Nkosi, Jonathan Glickman, Antonio Delgado-Gonzalez, Georg K. Gerber, Mike Angelo, Alex K. Shalek, Garry P. Nolan () and Sizun Jiang ()
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Bokai Zhu: Ragon Institute of MGH, MIT, and Harvard
Yunhao Bai: Broad Institute of MIT and Harvard
Yao Yu Yeo: Harvard Medical School
Xiaowei Lu: Stanford University
Xavier Rovira-Clavé: Stanford University
Han Chen: Stanford University
Jason Yeung: Harvard Medical School
Dingani Nkosi: Massachusetts General Brigham
Jonathan Glickman: Massachusetts General Brigham
Antonio Delgado-Gonzalez: Stanford University
Georg K. Gerber: Harvard Medical School
Mike Angelo: Stanford University
Alex K. Shalek: Ragon Institute of MGH, MIT, and Harvard
Garry P. Nolan: Stanford University
Sizun Jiang: Broad Institute of MIT and Harvard

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: Abstract The intricate interactions between the host immune system and its microbiome constituents undergo dynamic shifts in response to perturbations to the intestinal tissue environment. Our ability to study these events on the systems level is significantly limited by in situ approaches capable of generating simultaneous insights from both host and microbial communities. Here, we introduce Microbiome Cartography (MicroCart), a framework for simultaneous in situ probing of host and microbiome across multiple spatial modalities. We demonstrate MicroCart by investigating gut host and microbiome changes in a murine colitis model, using spatial proteomics, transcriptomics, and glycomics. Our findings reveal a global but systematic transformation in tissue immune responses, encompassing tissue-level remodeling in response to host immune and epithelial cell state perturbations, bacterial population shifts, localized inflammatory responses, and metabolic process alterations during colitis. MicroCart enables a deep investigation of the intricate interplay between the host tissue and its microbiome with spatial multi-omics.

Date: 2025
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DOI: 10.1038/s41467-025-56237-7

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